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Updated: Jun 23, 2025
Author Spotlight: Exploring Sex-Specific Glial Signatures and Therapeutic Leads for Alzheimer's Disease
Published on: May 20, 2024
Single cell transcriptome analysis identified a unique neutrophil type associated with Alzheimer's disease
Xiaolin Zhang1, Guiqin He1, Yixuan Hu2,3
1Shanghai Key Laboratory of Psychotic Disorders, Brain Health Institute, National Center for Mental Disorders, National Center for Mental Disorders, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, 200030, China.
Background:
Neutrophils play an essential role in Alzheimer's disease (AD) pathology. However, the extent of their heterogeneity remains poorly explored, particularly in the context of developing novel therapies targeting these cells.
Results:
We investigate the population structure of neutrophils purified from peripheral blood samples of AD mice. Utilizing single cell RNA sequencing, we comprehensively map neutrophil populations into six distinct clusters and find that the Neu-5 subset is specially enriched in AD mice. This subset exhibits fewer specific granules and a lower mature score. Gene ontology (GO) analysis reveals that genes involved in cytokine-mediated signaling are downregulated in the Neu-5 cluster. Furthermore, we identify the Ccrl2 gene is specifically upregulated in this subgroup, which is confirmed by flow cytometry in AD mice. Finally, immunohistochemical staining indicates that CCRL2 protein is increased in the brains of AD mice.
Conclusions:
We identify a unique CCRL2 positive neutrophil cluster, that is specifically enriched in the peripheral blood of AD mice.
